2.07 Myeloproliferative disorders

Question 1

BCR-ABL1 positive

Answer 1

chronic myeloid leukaemia
+++ granulocytes
Philadelphia chromosome

Question 2

BCR-ABL1 negative

Answer 2

idiopathic myelofibrosis
polycythaemia rubra vera
essential thrombocytopenia

Question 3

what disease should be considered:

• high granulocyte count
• high red cell count/hb
• high plts
• eosinophilia
• basophilia
• splenomegaly
• thrombosis in an unusual place
• no reactive explanation

Answer 3

myeloproliferative disease

Question 4

what is chronic myeloid leukaemia?

Answer 4

proliferation of myeloid cells
granulocytes + precursors
-other lineages= eg. platelets

Question 5

what is chronic phase CML?

Answer 5

intact maturation

3-5 years

Question 6

blast crisis of CML?

Answer 6

looks like acute leukaemia
maturation defect
fatal unless BMT an option

Question 7

clinical features of what disease:

• asymptomatic
• splenomegaly
• hypermetabolic symptoms
• gout
• priapism (hyperleucocytosis)

Answer 7

-CML

Question 8

lab findings of what disease:

• normal/low Hb
• leukocytosis with neutrophilia, myeloid precursors (myelocytes)
• eosinophilia
• basophilia
• thrombocytosis

Answer 8

CML

Question 9

bone marrow findings in CML?

Answer 9

increased myelocytes and eosinophils

Question 10

what is Philadelphia chromosome?

Answer 10

hallmark of CML
reciprocal translocation between long arms of chromosome 9/22

chromosome 22 make a fusion product

Question 11

what is the gene product of Philadelphia chromosome?

Answer 11

tyrosine kinase

abnormal signaling

Question 12

what drug is specific to Philadelphia chromosome gene products?

Answer 12

imatinib

Question 13

what are the features common to myeloproliferative diseases (BCR-ABL negative)

Answer 13

asymptomatic
increased cell turnover: gout, fatigue, weight loss, night sweats
splenomegaly symptoms
marrow failure- fibrosis or leukaemic transformation, lower PRV and ET
thrombosis- TIA, MIA, abdominal vessel thrombosis, claudication, erythromelalgia- red burning hot hands/feed continuous or episodic

Question 14

high Hb/HCT
erythrocytosis
(+- excess production of other lineages)

Answer 14

polycythaemia rubra vera

Question 15

secondary polycythaemia causes

Answer 15

chronic hypoxia
smoking
EPO tumour

Question 16

psudopolycythaemia causes

Answer 16

dehydration
diuretic therapy
obesity

Question 17

what explains pseudo polycythaemia?

Answer 17

there is less plasma and less packed red cells, underfilled bottle for chemical analysis(?)

Question 18

clinical features of what disease:

• MPD symptoms
• headache, fatigue
• itch- aquagenic pruritus

Answer 18

polycythaemia rubra vera

Question 19

JAK2 mutation

Answer 19

polycythaemia rubra vera
over 95% of these patients have this mutation
this mutation results in loss of autoinhibition (substitution mutation)
that causes activation of erythropoiesis in absence of ligand

Question 20

EPO level in PRV?

Answer 20

low

Question 21

PRV treatment goals:

Answer 21

venesection to maintain HcT

Question 22

uncontrolled production of abnormal platelets

• thrombosis
• bleeding at high levels due to acquired von willebrand disease

Answer 22

essential thrombocythaemia

Question 23

clinical features of what disease:

• MPD symptoms
• vasoocclusive complications
• bleeding- unpredictable esp at sx

Answer 23

essential thrombocythaemia

Question 24

what are reactive causes of thrombocytosis that must be excluded when considering ET?

Answer 24

blood loss
inflammation
malignancy
iron deficiency

also rule out CML

Question 25

What are the top 3 mutations in ET?

Answer 25

JAK2 mutation - 50%
CALr- calreticulin
MPL mutation

Question 26

Treatment of ET?

Answer 26

low risk- no tx, in young, no thrombosis

aspirin
cytoreductives: hydroxycarbamide, anagralide, interferon A

Question 27

what are the causes of myelofibrosis?

Answer 27

idiopathic -agnogenic myeloid metaplasia

post-polycythaemia or essential thrombocythaemia

Question 28

what are the signs of idiopathic myelofibrosis?

Answer 28

marrow failure 
bone marrow fibrosis 
liver and speen production of blooed
leukoerythroblastosis ****
tear drop shaped RBC in peripheral blood

Question 29

clinical features of what disease

• marrow failure: anaemia, bleeding, infection
• splenomegaly- LUQ pain, portal hypertension
• hypercatabolsim
• clinical changes of MPD

Answer 29

myelofibrosis

Question 30

lab diagnosis of what disease: 
tear drop shaped RBC =poikilocytes 
leucoerythroblastic
dry aspirate 
fibrosis in trephine biopsy 
jap2 or CALR mutation

Answer 30

myelofibrosis

Question 31

what are the 3 main causes of a leucoerythroblastic film?

Answer 31

erythroblasts- nucleated RBC
myelocytes

causes:
- reactive- sepsis
- marrow infiltration
- myelofibrosis

Question 32

Treatment of myelofibrosis?

Answer 32

supportive: blood transfusion, platelets, antibiotics
allogenic stem cell transplant in few people
?splenectomy

JAK2 inhibitors- may improve spleen size, QoL, ?survival?

Question 33

JAK2 inhibitor that treats myelofibrosis

Answer 33

ruxolitinib

Question 34

what are the reactive causes of high counts? (not MPD)

Answer 34

granulocytes

• infection- pyogenic bacteria causes neutrophilia
• physiology- post sx, steroids

platelets
-infection, iron deficiency, malignancy, blood loss

red cells

• dehydration, diuretics, pseudopolythythaemia
• secondary polycythaemia- hypoxia etc.